Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of neuronal function.
Phosphatidylserine synthase plays an essential role in glia and affects development, as well as the maintenance of neuronal function.
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磷脂酰丝氨酸合成酶在神经胶质细胞中起重要作用，影响神经细胞的发育和功能的维持。
DOI：
10.1016/j.isci.2021.102899
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发表时间：
2021-08-20
期刊：
影响因子：
5.8
通讯作者：
Jeon SH
中科院分区：
文献类型：
--
作者：
Park YJ;Kim S;Shim HP;Park JH;Lee G;Kim TY;Jo MC;Kwon AY;Lee M;Lee S;Yeo J;Chung HL;Bellen HJ;Kwon SH;Jeon SH
磷脂酰丝氨酸（PS）是真核细胞膜和细胞器的组成部分。果蝇基因组含有一个与哺乳动物PS合成酶同源的PS合成酶编码基因。具有Pss功能丧失等位基因的果蝇表现出寿命缩短、爆炸敏感性增加、运动缺陷和脑空泡化，这是与神经变性相关的迹象。我们观察到突变的成年人大脑中有缺陷的线粒体，以及活性氧的产生增加，自噬和凋亡细胞死亡增加。有趣的是，神经胶质特异性敲低或Pss的过度表达改变了幼虫阶段的突触发生和轴突生长，导致蛹阶段的发育停滞和成虫的神经变性。这在泛神经元上调或下调中未观察到。这些发现表明，精确调节Pss在胶质细胞中的表达是必不可少的发育和维持脑功能。我们提出了一种机制，这些神经退行性表型缺陷PS代谢引发的。Pss的缺失导致发育缺陷和神经退行性变Pss的缺失导致线粒体缺陷、ROS升高和继发性坏死Pss在神经胶质中的功能对于突触发生和神经元维持至关重要胶质细胞Pss的表达水平必须严格调节以维持健康的神经系统发育神经科学;细胞生物学;发育生物学
Phosphatidylserine (PS) is an integral component of eukaryotic cell membranes and organelles. The Drosophila genome contains a single PS synthase (PSS)-encoding gene (Pss) homologous to mammalian PSSs. Flies with Pss loss-of-function alleles show a reduced life span, increased bang sensitivity, locomotor defects, and vacuolated brain, which are the signs associated with neurodegeneration. We observed defective mitochondria in mutant adult brain, as well as elevated production of reactive oxygen species, and an increase in autophagy and apoptotic cell death. Intriguingly, glial-specific knockdown or overexpression of Pss alters synaptogenesis and axonal growth in the larval stage, causes developmental arrest in pupal stages, and neurodegeneration in adults. This is not observed with pan-neuronal up- or down-regulation. These findings suggest that precisely regulated expression of Pss in glia is essential for the development and maintenance of brain function. We propose a mechanism that underlies these neurodegenerative phenotypes triggered by defective PS metabolism. Loss of Pss leads to developmental defects and neurodegeneration Loss of Pss causes a mitochondrial defect, elevated ROS, and secondary necrosis Pss functions in glia are essential for synaptogenesis and neuronal maintenance Glial Pss expression level must be tightly regulated to maintain a healthy nervous system Developmental neuroscience; Cell biology; Developmental biology
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影响因子：
1.5
作者：
Hayashi, S;Ito, K;Goto, S
通讯作者：
Goto, S
影响因子：
3.9
作者：
Borisenko, GG;Matsura, T;Kagan, VE
通讯作者：
Kagan, VE
影响因子：
11.2
作者：
Gong, Yi;Sasidharan, Nikhil;Eichler, Florian
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Eichler, Florian
影响因子：
8.8
作者：
Hakim-Mishnaevski, Ketty;Flint-Brodsly, Naama;Kurant, Estee
通讯作者：
Kurant, Estee
影响因子：
4.8
作者：
Bergo, MO;Gavino, BJ;Young, SG
通讯作者：
Young, SG